safety of cetuximab and trifluridin tipiracil as the third-line therapy in the raswt mcrc

Conditions: Colorectal Neoplasms Malignant

Summary: this was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (tas-102) in the third-line treatment of chinese patients with ras wild-type mcrc.

this was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (tas-102) in the third-line treatment of chinese patients with ras wild-type mcrc. cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; after 1 cycle will be observed, and if ≤ 2 patients experience dlt, this dose level will be the recommended phase ii dose; if ≥ 3 patients experience dlt, additional 6 patients will receive dose level 0. ( dose level 0: 30 mg/m2, twice daily, days 1-5, once every 2 weeks;) if ≤ 2 individuals experience dlt, this dose level is the recommended phase ii dose; if ≥ 3 individuals experience dlt, the study will be stopped.

Eligibility criteria:
inclusion criteria: * 18-75 years old male or female; * histologically or cytologically confirmed metastatic colon or rectal adenocarcinoma; excluding appendiceal cancer and anal canal cancer; * previously received second-line treatment, at least 2 standard chemotherapy regimens(including fluorouracil, capecitabine, irinotecan, oxaliplatin, raltitrexed and anti-vegf, anti-egfr, etc.), if already accepted anti-egfr treatment achieved at least pr or above; * ecog ps 0-1; * at least one measurable lesion by ct or mri (according to recist 1.1 criteria, the longest diameter of tumor lesion ct/mri scan ≥ 10 mm, lymph node lesion ct/mri scan shortest diameter ≥ 15 mm); * ras gene mutation detection results are wild-type. the test sample can be the primary tumor or metastasis sample; * can receive oral drug treatment; * normal function of major organs, meeting the following criteria within 14 days before the start of treatment: 1. neutrophil count ≥ 1.5 × 10\*9/l; 2. platelet count ≥ 75 × 10\*9/l; 3. hemoglobin ≥ 9.0 g/dl; 4. ast ≤ 2.5 × unl (upper limit of normal) (if liver metastasis ast ≤ 5 × unl); 5. alt ≤ 2.5 × unl (if liver metastasis ast ≤ 5 × unl); g.creatinine clearance (calculated according to cockcroft and gault formula) \> 60 ml/min or serum creatinine ≤ 1.5 × unl; * expected survival time \> 3 months (90 days); * women of childbearing potential must have used reliable contraception and had a negative pregnancy test within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial and for 6 months after the last dose of trial drug. males must agree to use an adequate method of contraception or have been surgically sterilized during the trial and for 6 months after the last dose of trial drug; * the patients voluntarily participated in this study and signed the informed consent form, with good compliance and cooperation in the follow-up. exclusion criteria: * previously treated with regorafenib, fruquintinib, tas-102; * participated in another drug clinical trial in the past 4 weeks, or received systemic chemotherapy, radiotherapy or biological therapy in the past 4 weeks; * known brain metastases or strongly suspected brain metastases; * patients with known barf mutations should be excluded; * synchronous cancer or metachronous cancer with disease-free survival ≥ 5 years (except colorectal cancer), excluding mucosal cancer (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.) that has been cured or may be cured by local resection; * factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and gastric intestinal obstruction; ucontrolled crohn's disease or ulcerative colitis; * serosal effusion (including pleural effusion, ascites, pericardial effusion) with clinical symptoms and requiring symptomatic treatment; * pregnant or lactating women; patients of childbearing potential are unwilling or unable to take effective contraceptive measures; * known to be allergic to the study drug, study drug class and its ingredients; * conditions requiring systemic steroid treatment (except topical steroid and cetuximab pretreatment); * history of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or ct findings of interstitial lung disease; * active local or systemic infection requiring treatment; * cardiac function classification (nyha classification) ≥ grade iii or severe heart disease; * known history of human immunodeficiency virus (hiv) infection or acquired immunodeficiency syndrome (aids) or active hepatitis b, c; * toxicity not recovered (ctcae \> grade 1) or not completely recovered from previous anticancer surgery; * patients judged by the investigator as unsuitable for this study.